U.S. Pat. Nos. 4,350,271 and 3,995,632 describe dispensers that either absorb water and swell to dispense a lipophilic fluid or osmotically imbibe water to push a movable barrier which, in turn, dispenses a fluid which is liquid at temperature of use. Thus both inventions are similar in that lipophilic fluid is dispensed by means of a pressure generated by the interaction of water with a swellable polymer or with an osmotic agent. The instant invention is similar in function to these dispensers in that it also dispenses a lipid carrier by means of water imbibement and interaction with an osmotic agent. However, the instant invention is much different in structure and in mechanism of operation from these patented dispensers: (1) the osmotic agent and the lipid carrier are preferably present as a uniform mixture rather than being separated by a movable barrier or being present as separate layers, (2) the lipid carrier is preferentially released over the osmotic agent by means of preferential wetting of the inner surface of the polymeric wall by the lipid; intimate contact of the lipid carrier with the polymeric wall is aided by interfacial tension differences between the lipid carrier and the osmotic agent solution, formed by dissolution of the osmotic agent in the imbibed water; the lipid carrier is released through orifices or pores in said polymeric wall; and (3) the osmotic agent is released, secondary to the lipid carrier, whereas the swellable polymer and osmotic agent in the above-mentioned patented dispensers remain within the devices. The present invention thus has the advantage of being capable of releasing active agents in sequence, the first being released in the lipid carrier and the second being released in the osmotic agent solution. An active agent may, in fact, serve as the osmotic agent in this case. The instant invention can be easily configured in the form of tablets, devices, multiparticulate based dosage forms, and the like. Because of these unique properties, the instant invention having the ability to release active agents in sequence allows it to be utilized in a wider variety of applications in the controlled release of these agents.
The osmotic pump of the instant invention has the advantage that it is easier to make.
The present invention concerns an osmotically activated system for dispensing beneficial, preferably pharmacologically, active agents which have poor solubility in water. The system comprises an inner core compartment of active agent(s), lipid carrier(s) and osmotic agent(s) preferably in admixture, surrounded by an enclosing wall material. The core has the property that at the temperature of use, body temperature for pharmaceutical applications, the lipid carrier is or becomes fluid, and retains the active agent in a dissolved or suspended state. The wall consists of one or more polymer layers with the innermost layer being preferentially wetted by the lipid over the aqueous solution of osmotic agent(s). The wall constitutes a layer that is permeable to water and may or may not contain a permeability modifier and/or plasticizer. The lipid carrier containing the active agent is released from the system either via holes and/or pores in the wall as a result of water imbibition through the wall into the inner core compartment; the rate is controlled by the wall composition and dimensions. Sufficient osmotic agent is present to insure complete pumping of the lipid carrier at a controlled rate.
The object of this invention is to provide, for pharmaceutical applications, an osmotically activated system for the controlled delivery of pharmacologically active agents to the biological receptor sites over periods of time of preferably from 1 hour to several weeks.
The wall is the critical feature of the invention, not only providing a programmable fluid transport for controlled release of agent but the inner wall is preferentially wetted by the lipid carrier over the aqueous solution of osmotic agent(s) such that the lipid phase is pumped before the aqueous phase.
The preferential wetting of the wall by the lipid carrier provides a sufficient interfacial tension to prevent release of the aqueous phase until the lipid carrier has been pumped.
The wall may be composed of either insoluble, non-erodible materials mixed with leachable additives, or bioerodible materials containing leachable additives. Bioerodible materials would be selected to bioerode after a predetermined period with bioerosion occurring subsequent to the period of agent release.
Another object of the invention is to provide an osmotic system that is readily manufacturable to deliver a pre-determined dose of active agent(s) at a programmed rate from compositions of matter in the varied geometries and sizes of tablets, pellets, multiparticulates, and such related dosage forms as familiar to those skilled in the art of oral, buccal, vaginal, rectal, nasal, ocular, aural, parenteral and related routes of administration.
The key to the instant invention is not in the selection of the active agent(s) to be incorporated into the lipid, other than that it be substantially water insoluble and lipid soluble and/or lipid wettable. Likewise the key to the invention is not in the selection of the osmotic agent. The keys to the instant invention are the use of a water immiscible lipid carrier, which is liquid at the temperature of use, in particular body temperature, and in the specifications of the water insoluble wall.